Papillomaviruses are small DNA tumor viruses that infect animals and humans, causing primarily benign lesions. Certain papillomaviruses are also associated with cancer; the association of certain anogenital papillomaviruses with human cervical cancer is of clinical importance. Dr. Paul F. Lambert's laboratory is addressing two discrete areas in papillomavirus research. First, they are defining the mechanisms by which papillomaviruses regulate their gene expression and DNA replication. This is approached through the study of bovine papillomavirus type 1 (BPV-1), a prototype papillomavirus for molecular genetic analysis. Specifically studied are the viral E1 and E2 multi- gene families which are implicated in the regulation of viral transcription and plasmid replication. The E1 genes will be analyzed through a series of genetic and biochemical studies to define more precisely their functions in viral DNA replication and in viral transcription. The E2 genes will be analyzed primarily through biochemical approaches to better understand their mechanism of action in regulating viral transcription and plasmid DNA replication. The second area of research in Dr. Lamber's laboratory is the study of the role of papillomaviruses in the evolution of frank tumors in humans. Specifically studied is human papillomavirus type 16 (HPV-16), which is associated most often with cervical cancer. Experiments are aimed at generating and characterizing model systems that will allow Dr. Lambert to address the role of viral and cellular genes in tumorigenicity. These genetic studies are designed around the use of two reagents: transgenic mice, established in Dr. Lambert's laboratory, that express the HPV-16 E6-E7 oncogenes; and HPV-16-infected human cervical epithelial cells derived from a CIN I lesion.